The effects of birth timing and ambient temperature on the hypothalamic-pituitary-adrenal axis in 3-4 month old rhesus monkeys.

Birth timing, a relative measure of the timing of births within a season, has been shown to be related to the ways mothers and infant interact as well as to infant behavior and physiology. Although effects of birth timing on the hypothalamic-pituitary-adrenal (HPA) axis have previously been associated with variation in social relationships, these effects could also be related to seasonal variation in climate conditions when the birth season is long. The current study examines the effects of birth timing and ambient temperature on the activity and regulation of the HPA axis in 3-4 month old rhesus monkeys (N=338). Subjects were part of a BioBehavioral Assessment in which infants were separated from their mothers and relocated to a novel testing environment for a period of 25h. Four blood samples were collected and assayed for cortisol concentrations and reflected HPA response to (1) 2h maternal separation and relocation, (2) 7h maternal separation and relocation (sustained challenge), (3) dexamethasone suppression, and (4) ACTH challenge. Nonlinear mixed modeling was used to examine the independent effects of birth timing and temperature on HPA axis activity and regulation over the study period. Results indicated that birth timing and ambient temperature both had significant, but opposing effects on the cortisol response to sustained challenge. Chronic exposure to low ambient temperatures was associated with higher cortisol levels. After controlling for the effect of ambient temperature, birth timing was positively associated with cortisol such that late-born infants exhibited higher cortisol concentrations than did early-born infants. These results highlight the fact that climate conditions, even mild, subtropical conditions, can have potentially important influences on the activity and development of the HPA axis.

Vandeleest JJ ，Blozis SA ，Mendoza SP ，Capitanio JP ... -  《-》

Social stability influences the association between adrenal responsiveness and hair cortisol concentrations in rhesus macaques.

Hair cortisol concentrations are increasingly being used in both humans and nonhuman animals as a biomarker of chronic stress. However, many details regarding how hair cortisol concentrations relate to the dynamic activity and regulation of the HPA axis are still unknown. The current study explores 1) how the regulation of the HPA axis in infancy relates to hair cortisol concentrations (HCC) in infancy 2) whether this relationship persists into adulthood under conditions of social stability, and 3) how social instability impacts these relationships. All subjects were rhesus monkeys housed in large social groups at the California National Primate Research Center, and all had participated in a 25-hr. long BioBehavioral Assessment (BBA) at 3-4 months of age when four plasma samples were taken to assess HPA regulation, in particular cortisol responses to 1) 2-hour social separation and relocation, 2) sustained challenge, 3) dexamethasone and 4) ACTH administration. In Study 1, hair samples were collected at the end of the BBA testing from 25 infant rhesus monkeys from 2 different stable social groups. In Study 2, hair samples were obtained at three timepoints from 108 adults from 3 different stable social groups (1 in the Spring/Summer and 2 in the Fall/Winter) to examine the temporal stability of the relationship between HCC and HPA axis regulation. In Study 3, subjects included 31 infants and 33 adults from a single social group experiencing social instability following the same procedures as in Studies 1 and 2. Generalized linear models were used to determine if infants' HPA axis activity and regulation predicted HCC in infancy (Study 1), in adulthood with animals living in stable social conditions (Study 2) or in animals living in an unstable social group (Study 3). Results indicated that for both infants and adults living in stable social groups, HCC are associated with the adrenal response to ACTH in infancy. Samples collected in the winter also had higher HCC than those collected in summer. In the unstable social group, adult hair cortisol levels were higher than in the stable social groups. Additionally, there were no consistent relationships between HCC and infant HPA axis regulation among adults or infants living in a group experiencing social instability. These results suggest that the aspects of the HPA axis that drive HCC may differ depending on context. Under stable, non-stressed conditions there seems to be a trait-like association between adrenal responsivity and HCC in infancy and adulthood. However, this association may be reduced or eliminated under conditions of social stress.

Vandeleest JJ ，Capitanio JP ，Hamel A ，Meyer J ，Novak M ，Mendoza SP ，McCowan B ... -  《-》

OPRM1 gene variation influences hypothalamic-pituitary-adrenal axis function in response to a variety of stressors in rhesus macaques.

The endogenous opioid system is involved in modulating a number of behavioral and physiological systems, including the hypothalamic-pituitary-adrenal (HPA) axis. In humans, a functional variant in the OPRM1 gene (OPRM1 A118G) is associated with a number of outcomes, including attenuated HPA axis responses to stress. A nonsynonymous variant (OPRM1 C77G) in the rhesus macaque has been shown to have similar effects in vivo to the human variant. The current study investigated whether OPRM1 C77G influences HPA axis response to stress in rhesus macaques. We analyzed plasma adrenocorticotropic hormone (ACTH) and cortisol levels measured in response to three different stressors: (1) maternal separation in infant subjects at 6 months of age, (2) acute ethanol administration in adolescent subjects at 4 years of age, and (3) postpartum HPA axis function in adult rhesus macaque females. For the maternal separation paradigm, ACTH and cortisol levels were determined at baseline as well as peak levels during each of 4 consecutive separation episodes. For the acute ethanol administration paradigm, hormone levels were determined at baseline and again at 5 min, 10 min, and 60 min following the ethanol infusion. For postpartum sampling, hormone levels were determined at postpartum days 7, 14, 21, 30, 60, 90, 120, and 150. Infants carrying the 77G allele exhibited lower levels of cortisol across all 4 separation episodes. Furthermore, adolescents carrying the 77G allele exhibited lower cortisol levels at 5 and 10 min following acute ethanol administration. Adult females with prior reproductive experience and who carry the 77G allele exhibited lower cortisol levels across the postpartum period. No significant genotype effects were found for ACTH, although there were some trends for lower ACTH levels in 77G allele carriers. These data are consistent with human studies that have demonstrated attenuated cortisol responses to stress among carriers of the OPRM1 118G allele, lending further support to the argument that the rhesus and human allelic variants are functionally similar. Our results also suggest that OPRM1 variation may influence coping style, as well as alcohol-induced and postpartum levels of HPA axis activity and, as such, may modify vulnerability to alcohol use disorders and postpartum depression.

Schwandt ML ，Lindell SG ，Higley JD ，Suomi SJ ，Heilig M ，Barr CS ... -  《-》

Effects of rearing condition on HPA axis response to fluoxetine and desipramine treatment over repeated social separations in young rhesus monkeys.

Clarke AS ，Kraemer GW ，Kupfer DJ 《PSYCHIATRY RESEARCH》

Do neonatal bilateral ibotenic acid lesions of the hippocampal formation or of the amygdala impair HPA axis responsiveness and regulation in infant rhesus macaques (Macaca mulatta)?

Goursaud AP ，Mendoza SP ，Capitanio JP 《BRAIN RESEARCH》